The invention is relative to an orally applicable carbamazepine medicament with retarded active substance release. Carbamazepine, a 5 H-dibenz(b,f)azepine-5-carboxamide, is used in particular as an antiepileptic. Commercial forms of administration are tablets with 200 mg active substance, delayed-action tablets with 200 to 600 mg active substance and syrups.
It is known that carbamazepine very rapidly forms a dihydrate upon contact with water. This dihydrate is present in a crystalline form as needles which can grow up to a particle size of 500 .mu.m. This has a negative effect on the further processing, especially when developing retarding coatings. The known methods of production therefore do not use aqueous media and prefer to use organic solvents.
The retarding of an active substance can take place in various ways. DE patent 23 77 520 describes a formulation for carbamazepine in which the active substance is mixed with customary inactive tableting ingredients and pressed to a core or filled into capsules. The core or the capsule is coated with a methacrylic acid-methacrylic acid methylester mixture dissolved in isopropanol which mixture contains acetyltributylcitrate as softener. In this manner the forming of dihydrate by carbamazepine is prevented by the use of an organic solvent.
DE patents 38 68 077 and 37 25 824 claim a carbamazepine inactive ingredient composition containing a protective colloid which inhibits the crystalline growth of carbamazepine in the presence of water. The carbamazepine-containing core is coated in them with an organic solvent of cellulose acetate. A passage in the form of a perforation is placed in the film in a suitable manner.
The methods of producing these formulations have the disadvantage that the work must be carried out with organic solvents, which impacts the environment and signifies great effort and expense.
Furthermore, these medicaments produced as described above (tablets and capsules) are not divisible, since the casing is damaged in a division and the retarding action is lost therewith. Thus, the dosing possibilities are limited.
In addition, preparations (tablets) are known which do not lose their retarding action in a division or a disintegration into individual particles in liquids outside of or within the gastrointestinal tract. Pharm. Ind. 55, No. 10 (1993) pp. 940-947 describes compact oral preparations in which individual particles are coated with aqueous dispersions of copolymers of methacrylic acid and methylmethacrylic acid esters and pressed to tablets. The addition of 25-50% inactive ingredients brings about a more rapid decomposition of the tablets. The addition of a softener makes it possible to considerably increase the elongation at break of the coating and assures the mechanical stability. The coating of paracetamol-, potassium chloride- and acetylsalicylic acid active substance crystals, theophylline granulate and indomedacine and theophylline pellets are cited in this connection.
The present invention has the problem of making available a carbamazepine medicament in which, in spite of the use of water as solvent or dispersing agent, the crystal growth associated with the formation of dihydrate by the carbamazepine is prevented and the release of the carbamazepine is sufficiently retarded.